1. Field of This Invention
This invention is related to the production of 2-(2-aminothiazole-4-yl)-2-(syn)-methoxyimino acetic ester which, together with its derivatives, forms side chains of semisynthetic cephalosporins of the third generation. As such, these substances are of increasing importance.
2. Prior Art
In the case of the previously known production processes, one can differentiate between three synthesis ways. German patent document (open to public inspection) Nos. 28 12 625 and 28 31 332 or the French patent application Nos. 2,390,442 and 2,384,781, teach the following synthesis route: The acetoacetic ester is oximized, halogenated and reacted with thiourea into hydroxyiminothiazole acetic ester. The latter is then converted with diazomethane or dimethyl sulfate (without the use of the phase transfer catalysis of the process of this invention) into methoxyiminothiazolyl acetic ester.
German OS Nos. 27 15 385 and 28 05 655 disclose the following procedure: The oxyiminoacetoacetic ester is methylated, halogenated and then reacted with thiourea.
In the third synthesis method, the oxyiminoacetoacetic ester is first halogenated, then methylated and subsequently reacted with thiourea into methoxyiminothiazolyl acetic ester. This method of operation is taught by German OS No. 28 06 226 and the French patent application Nos. 2,381,053 and 2,384,779.
In the case of all of such synthesis methods, a mixture of syn- and anti-products is obtained: ##STR1## For use in connection with semisynthetic cephalosporins, i.e., for reaction with 7-aminocephalosporanic acid, however only the syn-isomeric is desired.